The Sialyl Lewis X Glycan Receptor Facilitates Infection of Subtype H7 Avian Influenza A Viruses

Guan, Minhui; Olivier, Alicia K.; Lu, Xiaotong; Epperson, William B.; Zhang, Xiaojian; Zhong, Lei; Waters, Kaitlyn; Mamaliger, Nataly; Li, Lei; Wen, Feng; Tao, Yizhi Jane; DeLiberto, Thomas J.; Wan, Xiu‐Feng

doi:10.1128/jvi.01344-22

Cited by 8 publications

(10 citation statements)

References 54 publications

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“…Although our results correlated with Zheng et al’s findings, validating the importance of the fucosylated glycans in the binding affinity of the omicron variant with the cell ACE2, the generated data suggest that the fucose unit may be part of a sialyl Lewis X epitope due to the large abundance of sialofucosylated N -glycans in comparison with the less abundant fucosylated N -glycans. This hypothesis also correlates with previous reports indicating that sialyl Lewis X glycan receptors facilitate viral infection [ 49 , 50 , 51 , 52 ].…”

Section: Discussionsupporting

confidence: 92%

N-Glycome Profile of the Spike Protein S1: Systemic and Comparative Analysis from Eleven Variants of SARS-CoV-2

Reyes,

Onigbinde,

Sanni

et al. 2023

Biomolecules

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The SARS-CoV-2 virus rapidly spread worldwide, threatening public health. Since it emerged, the scientific community has been engaged in the development of effective therapeutics and vaccines. The subunit S1 in the spike protein of SARS-CoV-2 mediates the viral entry into the host and is therefore one of the major research targets. The S1 protein is extensively glycosylated, and there is compelling evidence that glycans protect the virus’ active site from the human defense system. Therefore, investigation of the S1 protein glycome alterations in the different virus variants will provide a view of the glycan evolution and its relationship with the virus pathogenesis. In this study, we explored the N-glycosylation expression of the S1 protein for eleven SARS-CoV-2 variants: five variants of concern (VOC), including alpha, beta, gamma, delta, and omicron, and six variants of interest (VOI), including epsilon, eta, iota, lambda, kappa, and mu. The results showed significant differences in the N-glycome abundance of all variants. The N-glycome of the VOC showed a large increase in the abundance of sialofucosylated glycans, with the greatest abundance in the omicron variant. In contrast, the results showed a large abundance of fucosylated glycans for most of the VOI. Two glycan compositions, GlcNAc4,Hex5,Fuc,NeuAc (4-5-1-1) and GlcNAc6,Hex8,Fuc,NeuAc (6-8-1-1), were the most abundant structures across all variants. We believe that our data will contribute to understanding the S1 protein’s structural differences between SARS-CoV-2 mutations.

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Section: Discussionsupporting

confidence: 92%

N-Glycome Profile of the Spike Protein S1: Systemic and Comparative Analysis from Eleven Variants of SARS-CoV-2

Reyes,

Onigbinde,

Sanni

et al. 2023

Biomolecules

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“…In conclusion, Neu5Gc expression was absent in tissues tested from chicken, wild Canada geese, and gadwall, and was variable across the other wild duck species tested. As previously reported, all species expressed Neu5Ac (18,19).…”

Section: Distribution Of Neu5gc In the Respiratory And Gastrointestin...supporting

confidence: 85%

Neu5Gc binding loss of subtype H7 influenza A virus facilitates adaptation to gallinaceous poultry following transmission from waterbirds but restricts spillback

Guan,

Deliberto,

Feng

et al. 2024

Preprint

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Migratory waterfowl, gulls, and shorebirds serve as natural reservoirs for influenza A viruses, with potential spillovers to domestic poultry and humans. The intricacies of interspecies adaptation among avian species, particularly from wild birds to domestic poultry, are not fully elucidated. In this study, we investigated the molecular mechanisms underlying avian species barriers in H7 transmission, particularly the factors responsible for the disproportionate distribution of poultry infected with A/Anhui/1/2013 (AH/13)-lineage H7N9 viruses. We hypothesized that the differential expression of N-glycolylneuraminic acid (Neu5Gc) among avian species exerts selective pressure on H7 viruses, shaping their evolution and enabling them to replicate and transmit efficiently among gallinaceous poultry, particularly chickens. Our glycan microarray and biolayer interferometry experiments showed that AH/13-lineage H7N9 viruses exclusively bind to Neu5Ac, in contrast to wild waterbird H7 viruses that bind both Neu5Ac and Neu5Gc. Significantly, reverting the V179 amino acid in AH/13-lineage back to the I179, predominantly found in wild waterbirds, expanded the binding affinity of AH/13-lineage H7 viruses from exclusively Neu5Ac to both Neu5Ac and Neu5Gc. When cultivating H7 viruses in cell lines with varied Neu5Gc levels, we observed that Neu5Gc expression impairs the replication of Neu5Ac-specific H7 viruses and facilitates adaptive mutations. Conversely, Neu5Gc deficiency triggers adaptive changes in H7 viruses capable of binding to both Neu5Ac and Neu5Gc. Additionally, we assessed Neu5Gc expression in the respiratory and gastrointestinal tissues of seven avian species, including chickens, Canada geese, and various dabbling ducks. Neu5Gc was absent in chicken and Canada goose, but its expression varied in the duck species. In summary, our findings reveal the crucial role of Neu5Gc in shaping the host range and interspecies transmission of H7 viruses. This understanding of virus-host interactions is crucial for developing strategies to manage and prevent influenza virus outbreaks in diverse avian populations.Author SummaryMigratory waterfowl, gulls, and shorebirds are natural reservoirs for influenza A viruses that can occasionally spill over to domestic poultry, and ultimately humans. The molecular mechanisms underlying interspecies transmission and adaptation, particularly between wild birds and domestic poultry, remain poorly understood. This study showed wild-type H7 influenza A viruses from waterbirds initially bind to glycan receptors terminated with N-Acetylneuraminic acid (Neu5Ac) or N-Glycolylneuraminic acid (Neu5Gc). However, after enzootic transmission in chickens, the viruses exclusively bind to Neu5Ac. The absence of Neu5Gc expression in gallinaceous poultry, particularly chickens, exerts selective pressure, shaping influenza virus populations, and promoting the acquisition of adaptive amino acid substitutions in the hemagglutinin protein of H7 influenza A viruses. This results in the loss of Neu5Gc binding and an increase in virus transmissibility in gallinaceous poultry, particularly chickens. Consequently, the transmission capability of these poultry-adapted H7 viruses in wild water birds decreases. Timely intervention, such as stamping out, may help reduce virus adaptation to domestic chicken populations and lower the risk of enzootic outbreaks, including those caused by influenza A viruses exhibiting high pathogenicity.

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“…SLeX, mostly known to be involved in leukocyte binding, was identified in human respiratory tract tissue [ 8 ] including A549 cells [ 30 ] and shown to be recognized by different IAV subtypes [ 31 ]. In particular avian H7 IAVs [ 32 ]. The avian-origin FPV (not tested in [ 32 ]) was shown to recognize only the sulfated form of SLeX [ 31 ], which could explain the absence of binding in our experiments.…”

Section: Resultsmentioning

confidence: 99%

Relevance of Host Cell Surface Glycan Structure for Cell Specificity of Influenza A Viruses

Kastner

Karner

Zhu

et al. 2023

Viruses

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Influenza A viruses (IAVs) initiate infection via binding of the viral hemagglutinin (HA) to sialylated glycans on host cells. HA’s receptor specificity towards individual glycans is well studied and clearly critical for virus infection, but the contribution of the highly heterogeneous and complex glycocalyx to virus–cell adhesion remains elusive. Here, we use two complementary methods, glycan arrays and single-virus force spectroscopy (SVFS), to compare influenza virus receptor specificity with virus binding to live cells. Unexpectedly, we found that HA’s receptor binding preference does not necessarily reflect virus–cell specificity. We propose SVFS as a tool to elucidate the cell binding preference of IAVs, thereby including the complex environment of sialylated receptors within the plasma membrane of living cells.

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The Sialyl Lewis X Glycan Receptor Facilitates Infection of Subtype H7 Avian Influenza A Viruses

Abstract: In addition to causing outbreaks in domestic poultry, subtype H7 IAVs can cause sporadic spillover infections in lower mammals and humans. In this study, we showed that SLe X expression varies among wild dabbling ducks.

Cited by 8 publications

References 54 publications

N-Glycome Profile of the Spike Protein S1: Systemic and Comparative Analysis from Eleven Variants of SARS-CoV-2

N-Glycome Profile of the Spike Protein S1: Systemic and Comparative Analysis from Eleven Variants of SARS-CoV-2

Neu5Gc binding loss of subtype H7 influenza A virus facilitates adaptation to gallinaceous poultry following transmission from waterbirds but restricts spillback

Relevance of Host Cell Surface Glycan Structure for Cell Specificity of Influenza A Viruses

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